The main objective of this research is to aid in the design of new anti-tumor agents based on: 1) properties of the target enzymes thymidylate synthetase and dihydrofolate reductase, 2) structure of naturally occurring forms of folate and of folate analogs, 3) evaluation of presently available analogs as enzyme inhibitors and inhibitors of microbial growth, 4) pharmacology of folate and folate analogs. The following methods are to be employed: proton magnetic resonance, C13 magnetic resonance, 19F magnetic resonance, Laser Raman Spectroscopy, x-ray crystallography, ultra violet spectroscopy, enzyme kinetics, equilibrium dialysis, radioisotope exchange, microbiological assay.